Inhibition of tubulin polymerization is the target of many antitumoural agents known as antimitotic agents or spindle poisons colchicines, podophyllotoxins and combretastatins are representative examples of compounds that inhibit microtubule assembly by binding to tubulin. Benzothiazoles are small synthetic molecules that contain a benzene ring fused to a thiazole ring. These simple molecules have shown remarkable antitumour properties and some of them are undergoing evaluation in clinical trials (Shi, D.-F.; Bradshaw, T. D.; Wrigley, S.; McCall, C. J.; Lelieveld, P.; Fichtner, I.; Stevens, M. F. G. J. Med. Chem. 1996, 39, 3375; Kashiyama, E.; Hutchinson, I.; Chua, M.-S.; Stinson, S. F.; Phillips, L. R.; Kaur, G.; Sausville, E. A.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J. Med. Chem. 1999, 42, 4172; Hutchinson, I.; Chua, M.-S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.; Westwell, A. D.; Stevens, M. F. G. J. Med. Chem. 2001, 44, 1446). Recently Westwell and coworkers have prepared a series of benzothiazole derivatives and evaluated for anticancer activity, One of these analogues has shown excellent anticancer activity (Mortimer, C. G.; Wells, G.; Crochard, J.-P.; Stone, E. L.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. J. Med. Chem. 2006, 49, 179). Many chalcone, pyrazoline pyrazoline, isoxazole and isoxazoline type moieties related to combretastain A-4 showed potential biological properties particularly anticancer activity (Sylvie Ducki, David Rennison, Meiko Woo, Alexander Kendall, Jérémie Fournier Dit Chabert, Alan T. McGown, Nicholas J. Lawrence. Bioorg. Med. Chem, 17, 2009, 7698-7710; Regan LeBlanc, John Dickson, Toni Brown, Michelle Stewart, Hari N. Pati, Don VanDerveer, Hadi Arman, Jeff Harris, William Pennington, Herman L. Holt Jr., Moses Lee. Bioorg. Med. Chem, 13, 2005, 6025-6034; Marlie Johnson, Brent Younglove, Lauren Lee, Regan LeBlanc, Herman Holt Jr., Patrice Hills, Hilary Mackay, Toni Brown, Susan L. Mooberry, Moses Lee. Bioorg. Med. Chem. Lett, 17, 2007, 5897-5901; B. A. Bhat, K. L. Dhar, S. C. Puri, A. K. Saxena, M. Shanmugavel, G. N. Qazi. Bioorg. Med. Chem. Lett, 15, 2005, 3177-3180; Simoni, D.; Grisolia, G.; Giannini, G.; Roberti, M.; Rondanin, R.; Piccagli, L.; Baruchello, R.; Rossi, M.; Romagnoli, R.; Invidiata, F. P.; Grimaudo, S.; Jung, M. K.; Hamel, E.; Gebbia, N.; Crosta, L.; Abbadessa, V.; DiCristina, A.; Dusonchet, L.; Meli, M.; Tolomeo, M. J. Med. Chem. 2005, 48, 723, Julia Kaffy, Rene'e Pontikis, a, Danie'le Carrez, b Alain Croisy, Claude Monnereta, Jean-Claude Florent. Bioorg. Med. Chem. 2006, 14, 4067-4077, Gian Ceasure Tron, Tracy Pirali, Giovanni sorba, Francesca pagliai, Sara Buasacca, Armado A. Genazzani. J. Med. Chem. 2006, 49, 3033-3044. Tracey Pirali, Sara buasacca, Lorena Beltrami, Daniela Imovilli, Francesca Paliai, Gianluca Migilio, Alberto Massrotti, Luisella Verotta, Gian Cesare Tron, Givanni Sorba, Armado A. Genazzani. J. Med. Chem. 2006, 49, 5372-5376). Some of the heterocyclic bridged Combretastains showed an attractive profile of cytotoxicity and were able to induce apoptosis at lower concentrations.
